The RAB GTPase RAB18 modulates macroautophagy and proteostasis

• DOI: 10.1016/j.bbrc.2017.03.112
• Publication Date: 2017-03-22T17:08:15Z
• Authors: Anne Feldmann; Fazilet Bekbulat; Heike Huesmann; Sarah Ulbrich; Jörg Tatzelt; Christian Behl; Andreas Kern
• Keywords: 0303 health sciences; Protein Stability; Recombinant Fusion Proteins; rab3 GTP-Binding Proteins; Primary Cell Culture; Biophysics; Cell Biology; Fibroblasts; Biochemistry; Luminescent Proteins; 03 medical and health sciences; Gene Expression Regulation; Genes, Reporter; rab GTP-Binding Proteins; Proteolysis; Autophagy; Humans; RNA, Small Interfering; Molecular Biology; Signal Transduction; Red Fluorescent Protein

Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positive modulator of autophagy and is relevant for the maintenance of cellular proteostasis.